Effectiveness and Safety of Ustekinumab for Pediatric Inflammatory Bowel Disease: A Systematic Review.

BACKGROUND: The use of ustekinumab in pediatric patients with inflammatory bowel disease (IBD) is off-label and the data are limited. We conducted a systematic review evaluating the efficacy and safety of ustekinumab in pediatric IBD. METHODS: We systematically searched PubMed, EMBASE and Cochrane databases for studies of ustekinumab in children and adolescents with IBD investigating clinical remission, clinical response, corticosteroid-free (CS-free) remission, endoscopic remission/response, or safety up to March 17, 2023. A random-effects model was used for calculating summary estimates. RESULTS: Eleven studies, comprising 370 patients were included. For Crohn's disease (CD), the pooled clinical remission rates were 34% (73/204) at 8-16 weeks and 46% (60/129) at 1 year. The pooled CS-free clinical remission rates were 23% (10/44) at 8-16 weeks and 45% (42/96) at 1 year. For ulcerative colitis (UC)/IBD unspecified (IBD-U), the pooled CS-free clinical remission rates were 24% (6/25) at 26 weeks and 46% (16/35) at 1 year. Endoscopic remission was found in 0-37.5% of CD and 63.6% of UC. Serious adverse events were reported in 3.5% of patients. About one half of patients required reduction in dose intervals and 62.75% patients could continue ustekinumab therapy at 1 year or final visit. CONCLUSIONS: According to low-quality evidence mainly from cohort studies and case series, approximately one half of patients with CD and UC/IBD-U achieved remission at 1 year. Ustekinumab has a reasonable safety profile and dose optimization is frequently required. Data on the long-term benefit and high-quality evidence are still needed.

A Highly Effective, UV-Curable, Intumescent, Flame-Retardant Coating Containing Phosphorus, Nitrogen, and Sulfur, Based on Thiol-Ene Click Reaction.

In this paper, a flame-retardant, UV-cured coating was prepared on the fiber composites' (FC) surface via a thiol-ene click reaction using pentaerythritol tetra(3-mercaptopropionate) (PETMP), triallyl cyanurate (TAC), and 2-hydroxyethyl methacrylate phosphate (PM-2). The synergistic effectiveness of phosphorus (P), nitrogen (N), and sulfur (S) was studied in detail by changing the proportion of these reactants. Sample S4(N3P2)6, with a molar ratio of N and P elements of 3:2, and the thiol and vinyl groups of 4:6 had the highest LOI value (28.6%) and was self-extinguishing in the horizontal combustion test. It had the lowest peak heat release rate (PHRR) value (279.25 kW/m2) and total smoke production (2.18 m2). Moreover, the thermogravimetric analysis (TG) showed that the decomposition process of the coated composites was delayed. The conversion rate of the double bond and the thiol of S4(N3P2)6 was 100% and 92.0%, respectively, which showed that the cross-linked network structure was successfully formed. The tensile strength and the flexural strength of coated composites improved, and the transparency of the coating can reach 90%. These characteristics showed that the UV-cured coatings could be used in industrial production to effectively prevent fires.

Efficacy and safety of vedolizumab for pediatrics with inflammatory bowel disease: a systematic review.

BACKGROUND: Vedolizumab use in pediatrics is still off-label and the data are limited. We conducted a systematic review evaluating the efficacy and safety of vedolizumab in children and adolescents with inflammatory bowel disease (IBD). METHODS: PubMed, EMBASE and Cochrane databases were systematically searched for studies of vedolizumab in children and adolescents with IBD reporting clinical remission, response, corticosteroid-free (CS-free) remission, mucosal healing, or safety up to December 3rd 2021. RESULTS: Ten studies, comprising 455 patients were included. For CD, the pooled clinical remission rates were 25% (19/75) at 6 weeks, 28% (25/85) at 14 weeks, 32% (17/53) at 22 weeks, and 46% (43/92) at 1 year. For UC/IBD-U, the pooled clinical remission rates were 36% (25/70) at 6 weeks, 48% (52/101) at 14 weeks, 53% (24/45) at 22 weeks, and 45% (50/112) at 1 year. Mucosal healing was found in 17%-39% of CD and 15%-34% of UC/IBD-U respectively. Six percent of patients reported serious adverse events. CONCLUSIONS: According to low-quality evidence based on case series, approximately one-third and one-half of patients for CD and UC/IBD-U respectively achieved remission within 22 weeks, and about half of patients achieved remission at 1 year with reasonable safety profile. Long-term benefit profile data and high quality evidence are still needed.

Risk factors for Clostridioides difficile infection in children and adolescents with inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: Risk factors and consequences associated with Clostridioides difficile infection (CDI) in children and adolescents with inflammatory bowel disease (IBD) are still uncertain. We conduct a systematic review and meta-analysis to assess risk factors and outcomes associated with CDI in children and adolescents with IBD. METHODS: PubMed, EMBASE and Cochrane Library databases were searched from inception to 24th February, 2021. Studies investigating risk factors, bowel surgery rate in pediatric IBD patients with and without CDI were included. Random-effects model was used for calculating summary estimates. Newcastle-Ottawa scale (NOS) was used for quality assessment. RESULTS: Fourteen studies, comprising 17,114 patients, were included. There was a significant association between 5-aminosalicylic acid (5-ASA) use and CDI [odds ratio (OR) = 1.95, 95% confidence interval (CI) 1.26-3.03], with minimal heterogeneity (I2 = 0.00%). Increased risk of active disease (OR = 4.66, 95% CI 2.16-10.07) were associated with CDI in those studies performed in high quality score (NOS > 6) and significantly higher CDI rates in studies conducted outside USA (OR = 2.94, 95% CI 1.57-5.58). The bowel surgery rate in IBD with CDI was 3.8-57.1%, compared to that in IBD without CDI (0-21.3%). All studies were of moderate to high quality. CONCLUSIONS: 5-ASA use and active disease might be risk factors associated with CDI in children and adolescents with IBD. Bowel surgery rates associated with CDI in IBD patients varied greatly. Large-scale clinical studies on CDI in children and adolescents with IBD are still needed to verify risk factors and outcomes.

Randomized clinical trial: efficacy and tolerability of two different split dose of low-volume polyethylene glycol electrolytes for bowel preparation before colonoscopy in hospitalized children.

BACKGROUND: Eighty milliliter per kilogram of polyethylene glycol (PEG) for bowel preparation (BP) has been recommended, but the amount of liquid orally without nasogastric intubation is difficult to achieve. This study is to compare the efficacy and tolerability of two different low-volume PEG electrolyte solutions for BP in children. METHODS: The randomized, double-blind, controlled trial enrolled 150 children aged 6-18 years undergoing colonoscopy in our center. Patients were randomly assigned to receive 60 ml/kg (PEG-ELS 60) or 40 ml/kg (PEG-ELS 40) of PEG electrolytes (PEG-ELS) 4000. The Boston Bowel Preparation Scale was used for bowel cleansing evaluation. Primary end point was overall colon cleansing. Tolerability was also evaluated. RESULTS: PEG-ELS 40 and PEG-ELS 60 had similar efficacy in bowel cleansing for both whole colon and various colonic segments. The proportions of patients experiencing any adverse symptoms, or those who were willing to have BP repeated if necessary were similar in both groups. More patients considered the BP solution easy to take and be satisfied with the preparation in PEG-ELS 40 than PEG-ELS 60. CONCLUSIONS: Low volume of PEG-ELS for BP has good efficacy in bowel cleansing. PEG-ELS with 40 ml/kg volume was not inferior to that of 60 ml/kg. IMPACT: PEG-ELS 40 and PEG-ELS 60 had similar efficacy in bowel cleansing for whole and various colonic segments. The proportions of patients experiencing any adverse symptoms, or those who were willing to have BP repeated if necessary were similar in both groups. More patients considered BP solution easy to take and be satisfied with the preparation in PEG-ELS 40 than PEG-ELS 60. This study showed that low-volume PEG-ELS monotherapy was effective in bowel cleansing and explored a possibly feasible BP method for pediatrics in China that PEG-ELS 40 was comparable to PEG-ELS 60 regimen.

Retrospective study of budesonide in children with eosinophilic gastroenteritis.

BACKGROUND: The effectiveness of budesonide (BUD), a locally active steroid, on eosinophilic gastroenteritis (EGE) is not well understood. This study is to retrospectively evaluate the efficacy of BUD in children with EGE. METHODS: Forty-four children, diagnosed with EGE, were enrolled from 2013 to 2017 in our center. According to patients' preference, all the patients were treated with dietary elimination (DE) and montelukast therapy, or combined with prednisone (PRED)/BUD. Patients' clinical manifestations, treatments, and outcomes were reviewed from the medical records. Twenty-four patients (7 PRED, 7 BUD, 10 DE) received therapy for ≥8 weeks, followed by repeat endoscopy and biopsies. Histological response was defined as <20 eos/hpf (eosinophils per high-power field). RESULTS: Significant number of patients in DE+PRED (6/7, 85.7%) and DE+BUD (6/7, 85.7%) groups achieved histological response than in the DE group (3/10.30%) (p = 0.024). Mean post-treatment peak eos/hpf in the DE+PRED group was 16.57 ± 6.85 vs. 10.00 ± 5.07 in the DE+BUD group vs. 36.60 ± 24.57 in the DE group (p = 0.009). Change of eos/hpf from pre- to post-treatment was -49.86 ± 45.02 vs. -34.29 ± 23.44 in the BUD group vs. -0.3 ± 23.95 in the DE group (p = 0.011). There were no significant differences between DE+PRED and DE+BUD groups (p = 0.470, p = 0.363, respectively). CONCLUSION: BUD is effective in the treatment of EGE and has similar effectiveness with PRED.

Case report on alimentary tract hemorrhage and liver injury after therapy with oseltamivir: A case report.

RATIONALE: Oseltamivir-induced alimentary tract hemorrhage and liver injury are rarely reported in children and adult individuals. In this study, we described the clinical features and outcomes of oseltamivir-induced alimentary tract hemorrhage and liver injury in a child. PATIENT CONCERNS: Here, we present a case of a 6-year-old Asian boy with hematemesis and elevated alanine aminotransferase (ALT) (80 U/L) and aspartate aminotransferase (AST) (69 U/L) levels on day 2 of oseltamivir administration. The presence of alimentary tract hemorrhage and liver injury was diagnosed. The ALT level reached 1931.3 U/L, accompanied by an increase in total bilirubin (TBIL) to 53.3 µmol/L on day 15 after oseltamivir administration. Additional tests were performed to determine the presence of viruses that can cause hepatitis and autoantibodies, and the results from these tests were all negative. DIAGNOSIS: Drug-induced liver injury was considered. INTERVENTIONS: This patient was treated with compound glycyrrhizin and reduced glutathione and glucocorticoid. OUTCOMES: The liver enzymes recovered within 6 weeks without any symptoms of liver-related diseases after treatment with glucocorticoid. This treatment therefore helps reduce ALT and TBIL levels and protects the liver from further injury. LESSONS: Oral oseltamivir is widely used to treat influenza and the adverse effects of this drug were mostly mild. However, clinicians should always be alert for oseltamivir-induced alimentary tract hemorrhage and liver injury when prescribing oseltamivir for children.